Expression and localization of enzymes of arginine metabolism in the rat eye

Koshiyama, Yasuo; Gotoh, Tomomi; Miyanaka, Kei; Kobayashi, Tatsuhiko; Negi, Akira; Mori, Masataka

doi:10.1076/0271-3683(200004)2041-5ft313

Cited by 13 publications

(9 citation statements)

References 28 publications

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“…Although the exact ornithine metabolism in the eye is obscure, it seems to differ from that in the liver; proline oxidase and ornithine transcarbamylase are negligible in the eye (90,91) . Ornithine in the retina may be metabolised into proline by the cooperative action of OAT and pyrroline-5-carboxylate reductase and into putrescine by the action of ornithine decarboxylase.…”

Section: Discussionmentioning

confidence: 99%

“…Among bovine ocular tissues, arginase activity was high in the retina and uvea; pyrroline-5-carboxylate reductase activity was high in the lens, cornea and retina; pyrroline-5-carboxylate dehydrogenase activity was high in the uvea but low in the retina; and proline oxidase activity was negligible in all ocular tissues (90) . Koshiyama et al (91) reported that mRNA for ornithine transcarbamylase analysed by RT-PCR was not detected in the rat ocular tissues and that arginase II (nonhepatic-type) mRNA was detected in the retina and weakly in the cornea, whereas arginase I (hepatic-type) mRNA was not detected in rat eyes. Thus, the exact ornithine metabolism in the eye, particularly in the RPE, is unknown.…”

Section: Ornithine Metabolism In the Eyementioning

confidence: 99%

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Retinal risks of high-dose ornithine supplements: a review

2011

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We reviewed the literature on ornithine supplementation and related topics. Nutritionists and physicians have reported that ornithine supplementation is useful. Paediatricians and biochemists have reported that ornithine is supplemented for NH 3 detoxification in the hyperornithinaemia -hyperammonaemia -homocitrullinuria (HHH) syndrome. In contrast, ophthalmic researchers have reported retinotoxicity associated with high-dose ornithine. In vivo and in vitro experiments have shown that high concentrations of ornithine or its metabolites are toxic to the retinal pigment epithelial (RPE) cells. Long-term (exceeding a few years) and high concentrations (exceeding 600 mmol/l) of ornithine in the blood induce retinal toxicity in gyrate atrophy of the choroid and retina (GA). Intermittent high levels of ornithine do not lead to retinal lesions. Constant blood ornithine levels between 250 and 600 mmol/l do not induce retinal lesions or cause a very slowly progressive retinal degeneration. Blood ornithine levels below 250 mmol/l do not produce retinal alteration. We concluded that short-term, low-dose or transient high-dose ornithine intake is safe for the retina; its nutritional usefulness and effect on NH 3 detoxification are supported by many researchers, but the effect may be limited; and long-term, high-dose ornithine intake may be risky for the retina. Patients with GA should avoid taking ornithine; amino acid supplementation should be administered carefully for patients with the HHH syndrome, relatives of patients with GA (heterozygotes) and subjects with RPE lesions; and blood ornithine levels and retinal conditions should be evaluated in individuals taking long-term, high-dose ornithine.

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Section: Discussionmentioning

confidence: 99%

Section: Ornithine Metabolism In the Eyementioning

confidence: 99%

Retinal risks of high-dose ornithine supplements: a review

2011

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“…In contrast, arginine levels were dramatically increased in Müller cells following GS inhibition. Given that the brain and retina do not have a urea cycle and remove excess nitrogen via GS amidation of glutamate (Koshiyama et al. 2000; Wiesinger 2001), the likely explanation is a ‘flow back’ effect secondary to altered glutamate catabolism.…”

Section: Discussionmentioning

confidence: 99%

Glutamate metabolic pathways and retinal function

Bui

Acosta

et al. 2009

Journal of Neurochemistry

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Glutamate is a major neurotransmitter in the CNS but is also a key metabolite intimately coupled to amino acid production/degradation. We consider the effect of inhibition of two key glutamate metabolic enzymes: glutamine synthetase (GS) and aspartate aminotransferase on retinal function assessed using the electroretinogram to consider photoreceptoral (a‐wave) and post‐receptoral (b‐wave) amplitudes. Quantitative immunocytochemistry was used to assess amino acid levels within photoreceptors, ganglion and Müller cells secondary to GS inhibition. Intravitreal injections of methionine sulfoximine reduced GS immunoreactivity in the rat retina. Additionally, glutamate and its precursor aspartate was reduced in photoreceptors and ganglion cells, but elevated in Müller cells. This reduction in neuronal glutamate was consistent with a deficit in neurotransmission (−75% b‐wave reduction). Exogenous glutamine supply completely restored the b‐wave, whereas other amino acid substrates (lactate, pyruvate, α‐ketoglutarate, and succinate) only partially restored the b‐wave (16–20%). Inhibition of the aminotranferases using aminooxyacetic acid had no effect on retinal function. However, aminooxyacetic acid application after methionine sulfoximine further reduced the b‐wave (from −75% to −92%). The above data suggest that de novo glutamate synthesis involving aspartate aminotransferase can partially sustain neurotransmission when glutamate recycling is impaired. We also show that altered glutamate homeostasis results in a greater change in amino acid distribution in ganglion cells compared with photoreceptors.

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“…Argininosuccinate is the precursor of arginine which at the same time leads to urea in the urea cycle. This enzyme was detected in the eyes of rats as well as in other tissues [21], demonstrating its ubiquity and giving rise to the belief that its expression is dependent on the tissue needs (not like in the liver where it is continuously expressed). Koshiyama et al (2000) also showed that arginine recycling activity from citrulline was present in ocular tissues [21].…”

Section: Metabolomic Study With Patients With High and Low Myopiamentioning

confidence: 95%

Looking into aqueous humor through metabolomics spectacles − exploring its metabolic characteristics in relation to myopia

Barbas-Bernardos

Armitage

Garcı́a

et al. 2016

Journal of Pharmaceutical and Biomedical Analysis

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Aqueous humor is the transparent fluid found in the anterior chamber of the eye that provides the metabolic requirements to the avascular tissues surrounding it. Despite the fact that metabolomics could be a powerful tool in the characterization of this biofluid and in revealing metabolic signatures of common ocular diseases such as myopia, it has never to our knowledge previously been applied in humans. In this research a novel method for the analysis of aqueous humor is presented to show its application in the characterization of this biofluid using CE-MS. The method was extended to a dual platform method (CE-MS and LC-MS) in order to compare samples from patients with different severities of myopia in order to explore the disease from the metabolic phenotype point of view. With this method, a profound knowledge of the metabolites present in human aqueous humor has been obtained: over 40 metabolites were reproducibly and simultaneously identified from a low volume of sample by CE-MS, including among others, a vast number of amino acids and derivatives. When this method was extended to study groups of patients with high or low myopia in both CE-MS and LC-MS, it has been possible to identify over 20 significantly different metabolite and lipid signatures that distinguish patients based on the severity of myopia. Among these, the most notable higher abundant metabolites in high myopia were aminooctanoic acid, arginine, citrulline and sphinganine while features of low myopia were aminoundecanoic acid, dihydro-retinoic acid and cysteinylglycine disulfide. This dual platform approach offered complementarity such that different metabolites were detected in each technique. Together the experiments presented provide a whelm of valuable information about human aqueous humor and myopia, proving the utility of non-targeted metabolomics for the first time in analyzing this type of sample and the metabolic phenotype of this disease.

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Expression and localization of enzymes of arginine metabolism in the rat eye

Cited by 13 publications

References 28 publications

Retinal risks of high-dose ornithine supplements: a review

Retinal risks of high-dose ornithine supplements: a review

Glutamate metabolic pathways and retinal function

Looking into aqueous humor through metabolomics spectacles − exploring its metabolic characteristics in relation to myopia

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